This invention relates to compounds that demonstrate anti-oxidant and vascular properties, including vasodilation.
The antioxidant properties of various plant favonoids, including procyanidins, are well known. Procyanidins possess endothelium-dependent relaxing (EDR) activity in blood vessels in vitro. The original finding that red wines, grape juice and other grape products exhibited EDR activity was companied by strong evidence that this activity was due to stimulation of nitric oxide (NO) production by the endothelial cells which form the lining of all blood vessels. Vasorelaxation induced by grape extracts, wines and the like was reversed by NO synthase inhibitors, and vasorelaxation could be restored by exposure of the vessel to L-arginine, the normal substrate for NO synthase. The importance of nitric oxide synthase system is underscored by the finding that a dysfunctional NO system can contribute to several diseases, including atherosclerosis. Therefore, consumption (and absorption) of NO-stimulating compounds in the diet, or in the form of dietary supplements, could contribute to prevention or halting the progress of atherosclerosis, other chronic age-related diseases, or conditions known to involve failure of the NO/NO synthase system, e.g., erectile dysfunction. Although procyanidin compounds, particularly those from grape seed extracts are known to exhibit EDR activity, current supplements administered to patients and consumers do not identify, nor isolate the active and most potent compounds to achieve the desired EDR.
The present invention is an isolated compound and method of inducing endothelium-dependent relaxation in blood vessels including the step of introducing isolated procyanidins having a preponderance of (xe2x88x92)-epicatechins to a patient wherein the procyanidins are preferably galloylated. To achieve both bioavailability and potency, it is also preferred that the number of epicatechins monomers forming each procyanidin is between two and five. More specifically, isolated epicatechin-(4-8)epicatechin-(4-8)-epicatechin-gallate (C1-gallate) is administered to the patient. To enhance endothelium-dependent relaxation, a concomitant administration of L-arginine may be performed.